Can gastrodin calm RA by blocking histone lactylation?
Gastrodin bound KAT8 (KD 413.72 μM), lowered H3K9la, cut IL-6/MMP signals in FLS and THP-1 cells, and eased joint swelling in AIA rats at 20 mg/kg.
Source
Gastrodin attenuates rheumatoid arthritis by targeting KAT8 to inhibit the lactylation of H3K9
Study at a glance
- Design
- Animal / in-vitro — LPS-stimulated FLS/THP-1 cultures plus Sprague-Dawley rat adjuvant-induced arthritis; docking/SPR targeting KAT8
- N
- N=5 · AIA rats randomly grouped n=5 per group (AIA, GAS, DEX); plus in vitro FLS and THP-1 macrophage assays
- Population
- Rheumatoid-arthritis models: fibroblast-like synoviocytes, THP-1 macrophages, and SD rat AIA
- Outcome
- Inflammatory cytokines/MMPs, H3K9 lactylation, KAT8 stability, and joint swelling/synovial hyperplasia
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Inspect source passages
Can gastrodin calm RA by blocking histone lactylation?
These passages occur verbatim in the stored paper text. They support the points listed below; they do not verify every statement in the explanation.
GAS–KAT8 SPR dissociation constant was 413.72 μM.
Molecular docking and surface plasmon resonance (SPR) assays confirmed KAT8 as a direct target of GAS, with a dissociation constant ( K D ) of 413.72 μM.
In vivo GAS 20 mg/kg improved AIA joint swelling and synovial hyperplasia.
In vivo , GAS (20 mg/kg) ameliorated joint swelling and synovial hyperplasia in a Sprague-Dawley rat adjuvant-induced arthritis (AIA) model, correlating with decreased H3K9la and IL-6 expression.
What they did
Treated LPS-stimulated FLS and THP-1 macrophages with gastrodin (10–20 μM), confirmed KAT8 binding by docking and SPR, manipulated KAT8, and tested 20 mg/kg gastrodin in Sprague-Dawley AIA rats.
What they found
GAS inhibited IL-6, MMP1, and MMP13 via lower glycolysis/lactate. SPR KD was 413.72 μM. GAS destabilized KAT8 and reduced H3K9la. In AIA rats, 20 mg/kg lessened swelling and synovial hyperplasia with lower H3K9la and IL-6.
The limits
What it doesn't show
Cell and rat AIA data do not equal a human RA trial; micromolar SPR affinity is modest, so clinical dosing and safety are unproven.
Key terms
- Gastrodin (GAS)
- Phenolic glycoside from Gastrodia elata tested here as an RA candidate.
- KAT8
- Lysine acetyltransferase 8, a lactoyltransferase target of gastrodin.
- H3K9la
- Histone H3 lysine-9 lactylation linked to inflammatory gene programs.
- FLS
- Fibroblast-like synoviocytes that drive synovial inflammation in RA.
- AIA
- Adjuvant-induced arthritis rat model of inflammatory joint disease.
- SPR
- Surface plasmon resonance used to measure GAS–KAT8 binding (KD 413.72 μM).
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Gastrodin’s histone mark target was:
Common questions
What did gastrodin target?
KAT8, reducing H3K9 lactylation.
In-vitro concentrations?
10–20 μM in FLS and THP-1 macrophages.
Rat dose?
20 mg/kg in Sprague-Dawley AIA.
SPR affinity?
KD 413.72 μM for GAS–KAT8.
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